Annals of Human Biology, September –October 2012; 39(5): 402–411
Copyright q Informa UK, Ltd.
ISSN 0301-4460 print/ISSN 1464-5033 online
DOI: 10.3109/03014460.2012.704071
REVIEW
Human biology at the interface of paediatrics: Measuring bone mineral
accretion during childhood
Babette S. Zemel
Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia, The Perelman School of
Medicine, University of Pennsylvania, 3535 Market Street, room 1560, Philadelphia, PA 19104-4399, USA
Background: Professor Tanner established a paradigm for
the study of growth and development that demands precise
growth measurements, description of normal variability
through development to adulthood, consideration of the
effects of tempo and the study of factors that influence growth
outcomes. The relatively new field of paediatric bone health
assessment fits this paradigm and reflects the collaboration
of human biologists and paediatricians in understanding
the growth of the human skeleton.
Review: This review describes the reasons for clinical
assessment of bone density in children, the technological
developments in bone health assessment in children, the
development of reference curves and the effects of growth,
body composition, pubertal timing, genetics and lifestyle on
bone health outcomes.
Keywords: Growth charts, children, DXA, bone mineral content,
bone mineral density
INTRODUCTION: THE LEGACY OF PROFESSOR TANNER
The legacy that Professor Tanner created in the field of child
growth and development is unparallelled. Along with his
outstanding team and all those who trained with him, the
fields of paediatrics and human biology have enlightened
the understanding of the processes of human growth and the
assessment of growth status. Professor Tanner established a
standard for the study of growth and development. In broad
strokes, this standard defined the precision and detail with
which growth measurements were acquired, the collection of
large amounts of growth data to characterize variability in
growth, the development of growth charts for determining
growth status based on healthy children living in
environments to support optimal growth, the apprecia-
tion of growth tempo and longitudinal growth assessment
Correspondence: Babette Zemel, PhD, Division of Gastroenterology, Hepatology and Nutrition, The Children’s Hospital of Philadelphia,
The Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, room 1560, Philadelphia, PA 19104-4399, USA. Tel: 215-590-1669.
Fax: 215-590-0604. E-mail: zemel@email.chop.edu
(Received 15 March 2012; revised 17 May 2012; accepted 1 June 2012)
402
and the science that identified the many factors that
influence growth.
Over the last few decades, these scientific traditions have
continued. Reference charts for growth, such as the US
height charts (Kuczmarski et al. 2000) and UK charts
(Freeman et al. 1995) have been adopted since they better
represent contemporary growth patterns and have been
created using more current statistical methods (Cole and
Green 1992). International growth standards aimed at
identifying optimal growth have been developed for infants
and young children (de Onis et al. 2009) and for body mass
index in older children (Cole et al. 2000). Reference ranges
for other growth characteristics have also been established,
such as for lean tissue (Wells et al. 2010) and spirometry
(Stanojevic et al. 2008). Reference ranges for childhood bone
mass and density have also been developed and the details of
this progress underscore the legacy of Professor Tanner.
GROWTH AND DEVELOPMENT OF THE SKELETON
Over the past two decades, technological developments have
made it feasible to assess the growth of the skeleton. In
particular, the development of dual energy x-ray absorptio-
metry (DXA) and quantitative computed tomography
(QCT) have facilitated studies of skeletal development and
paediatric bone health (Leonard and Zemel 2002).
Anthropometric techniques for measuring skeletal dimen-
sions (Lohman et al. 1988) and radiologic techniques for
assessing skeletal maturation (Greulich and Pyle 1950;
Tanner et al. 2001) and radiogrammetry of cortical bone
(Spencer et al. 1966; Dequeker 1976) were established
decades ago. However, these techniques were not capable of
assessing the acquisition of bone mineral and the alterations
in bone composition and strength during growth.
 MEASURING BONE MINERAL ACCRETION DURING CHILDHOOD
In concert with somatic growth and increasing size of the
skeleton, bone mineral mass, density and bone architecture
also change with growth. Exquisitely complex cross-talk
between osteoblasts and osteoclasts is required to effect these
changes through the remodelling of existing bone and
modelling of new bone as bone growth proceeds. Bone is
comprised of the cartilaginous tissue at the joints, the
mineralized structure of cortical and trabecular of the long
and flat bones, marrow space and, in children, the calcified
cartilage in growth plates. As bones increase in length, they
also increase in width, so bone formation and resorption
must by appropriately co-ordinated to preserve structural
strength (Rauch 2007).
Childhood and adolescence are thought to be critical
periods for the development of bone mass. It is estimated
that more than half of the bone calcium is normally laid
down during the teen years (Bachrach 2001). As Professor
Tanner showed more than a quarter of a century ago, the
development of the skeleton is not uniform; the axial and
appendicular skeleton increase in size at different rates
(Tanner et al. 1976). Prior to puberty, there is proportion-
ately greater growth in the limbs than the trunk. The relative
rate of growth of the spine increases in early and mid-
puberty and growth slows at all sites in late puberty (Bass
et al. 1999; Bradney et al. 2000). Peak bone mineral accrual
lags behind growth in height by , 8 months (McKay et al.
1998; Bailey et al. 2000) and bone mineral accretion is
believed to continue into the 3rd decade of life (Lorentzon
et al. 2005; Baxter-Jones et al. 2011).
PAEDIATRIC BONE HEALTH ASSESSMENT
Due to advances in medical therapies, children with
complex medical conditions are surviving to adulthood
and experiencing significant improvements in life expect-
ancy. For example, for people with cystic fibrosis, a genetic
disorder primarily affecting the lungs and pancreas, the
mean age at death rose from 12 years to 28 years for
males and from 15 years to 25 years for females living in
Australia between 1979 and 2005 (Reid et al. 2011). Among
children born with congenital malformations of the heart in
Belgium, survival to adulthood increased from 81% among
the 1970 –1974 birth cohort to 89% among those born
1990 – 1992 (Moons et al. 2010). Along with improved
survival to adulthood, many complex medical conditions of
childhood pose threats to bone health, through primary
disease effects such as malabsorption, secondary effects such
as prolonged periods of physical inactivity or treatment
effects such as glucocorticoid therapy. There is also concern
that inadequate bone accretion during the critical period
of growth and maturation will result in fragile bones and
physical disability in adulthood (Heaney et al. 2000).
In otherwise healthy children, bone accretion is also a
public health concern. First and foremost, it is a widely
held belief that bone accretion during childhood is a
major determinant of bone health later in life. Osteoporosis
(or bone fragility) is one of the most common conditions
among older adults. The US Surgeon General Report on
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403
Osteoporosis (Office of the Surgeon General 2004)
estimated that 10 million Americans over age 50 have
osteoporosis. There is significant morbidity and mortality
associated with this disease and its relationship to fracture
risk, as 20% of senior citizens who suffer a hip fracture will
die within 1 year and others experience a downward spiral
in mental and physical health. In 2002, the economic cost
in direct care expenditures for osteoporotic fractures was
estimated at $12.2 – 17.9 billion each year. If osteoporosis
has origins in childhood, then understanding the factors
affecting bone accretion in childhood may be the key to early
prevention of this common, disabling condition.
Bone health and fracture prevention in childhood is also
a public health concern. Several studies estimate that 30% of
children will experience a fracture before reaching adult-
hood (Cooper et al. 2004). Childhood fractures most
commonly occur in the distal extremities, particularly the
forearm. Although not as debilitating as osteoporotic
fractures of the hip and spine among the elderly, this
childhood fracture rate is comparable to the lifetime fracture
risk of women over 50 in the UK (van Staa et al. 2001).
Factors associated with fracture during childhood include:
lower bone density, a previous fracture, European ancestry,
obesity and low dairy intake (Goulding et al. 2000, 2004;
Clark et al. 2006; Kalkwarf et al. 2011).
Threats to optimal bone mineral acquisition include
malabsorption, inflammation, decreased physical activity,
malnutrition, hypogonadism, delayed growth and matu-
ration, altered body composition and some medications
(Leonard and Zemel 2002). Many children with complex
medical conditions have one or more risk factors. Poor
growth, altered body composition and delayed maturation
are particularly common. For example, children with
Crohn’s disease, an inflammatory bowel disease, have low
height z-scores and muscle deficits relative to their short
stature compared to controls (Thayu et al. 2007). Low bone
density is common at disease presentation (Burnham et al.
2004; Dubner et al. 2009), even with adjustment for short
stature. Children with sickle cell disease, a genetic anaemia,
are small-for-age, have low BMI and significant muscle
deficits (Barden et al. 2002), delayed maturation (Zemel et al.
2007) and low bone density (Buison et al. 2005), even after
adjusting for short stature and low muscle mass. Among
children born pre-term, subsequent deficits in bone mineral
content during childhood are attributable to effects of
maturity, height, weight, physical activity and diet
(Erlandson et al. 2011); in adulthood, bone density deficits
are not evident (Breukhoven et al. 2011). At the other end of
the spectrum, obese children typically have higher bone
mass and density and larger, stronger bones (Leonard et al.
2004; Petit et al. 2005; Stettler et al. 2008). Body
composition, particularly muscle mass, is an important
determinant of bone health because of the response of bone
to mechanical stimuli and weight-bearing physical activity
(Schonau et al. 1998). Muscle mass is an excellent proxy of
the mechanical stimulation to bone and is highly correlated
to bone mass, density and architecture (Wetzsteon et al.
2011). Thus, among children with complex medical
404 B. ZEMEL
conditions it is difficult to determine the degree to which
bone deficits are attributable to altered growth and body
composition vs other disease-related factors.
Dual energy x-ray absorptiometry (DXA) is the most
widely used method for assessing bone mineral mass
and density. DXA uses a very low radiation beam that is
attenuated as it passes through the human body (Crabtree
et al. 2007). The degree of attenuation is determined by
the thickness and density of the tissue through which the
beam passes. Based on this principal, DXA estimates bone
mineral content (BMC, g), bone area (cm2) and areal bone
mineral density (aBMD, g/cm2) from a two-dimensional
(planar) collection of attenuation values. The DXA software
uses an algorithm to define the bone edge based on
distinctive changes in attenuation values and generates a
two-dimensional image of the bone and surrounding soft
tissue. Figure 1 shows bone DXA images for the total body,
lumbar spine and proximal femur.
DXA scans involve extremely low radiation (, 1 mSv)
and are rapid; depending on the site measured a single scan
may take 1 – 3 minutes on modern devices. Precision is
excellent and has been reported to be similar to adults
(Shepherd et al. 2011). From the standpoint of scan
acquisition, it is a safe, reliable and feasible procedure for
children. The history of the development of DXA for bone
health assessment in children is an illustrative tale of
the importance of accurate measurement technique, deve-
lopment of reference data and understanding the influence
of growth and maturation.
DEVELOPMENT OF DXA REFERENCE DATA
The original DXA reference data for Hologic bone
densitometers was based on a small study by Southard
et al. (1991). The study site was a single geographic
centre using an Hologic QDR 1000 pencil beam scanner.
Figure 1. DXA scan images for the total body, lumbar spine and proximal femur.
The sample was comprised of 218 children, 1 – 19 years of
age, 26% of whom were African American and only lumbar
spine measurements were obtained. The age-specific means
and standard deviations were used as reference values for
clinical assessment of bone health in children and
incorporated into the manufacturer’s software.
Subsequent studies of healthy children were conducted
and published including a large study of healthy Canadian
children of 8 – 17 years of age by Faulkner et al. (1993). This
study published sex- and age-specific means and standard
deviations for aBMD at multiple sites. To evaluate the
impact of using reference data that was not sex-specific,
Leonard et al. (1999) compared bone density z-scores for
groups of children at risk for poor bone acquisition using
the reference ranges from Southard et al. (1991), adopted by
Hologic, the Canadian reference data (Faulkner et al. 1996)
and others (Glastre et al. 1990; Bonjour et al. 1991;
Henderson and Madsen 1996). They showed the profound
impact of using reference ranges that are not sex-specific;
9 – 13% of girls and 24 –44% of boys were identified as
having low bone mass when non-specific reference ranges
were used compared to 10% of boys and 11 – 16% of girls
classified as low bone mass when age- and sex-specific
reference data were used (see Figure 2). The DXA
manufacturer subsequently revised the paediatric reference
ranges in their software to include the Canadian values for
children aged 8 – 17.
Simultaneous to these improvements in reference ranges,
DXA technology was advancing in the technical aspects of
measuring young children. This included a low density
software option for young children that used a different
threshold in the bone edge detection algorithm to
accommodate the lower attenuation values that occur in
measuring young children. This development also had a
profound impact on the measurements obtained (Leonard
et al. 1998). Z-scores decreased by 0.7, on average, with the
Annals of Human Biology
 MEASURING BONE MINERAL ACCRETION DURING CHILDHOOD 405

Figure 2. Diagnosis of osteopenia according to reference data source in children at-risk for low bone density. Figure adapted from Leonard et al.
(1999). Reference data sources from Southard et al. (1991). Glastre et al. (1990) and Henderson and Madsen (1996) were age- but not sex-specific,
whereas reference ranges provided by Bonjour et al. (1991) and Faulkner et al. (1996) were sex- and age-specific. Use of reference ranges in children
that did not take sex differences into account resulted in significantly greater prevalence of osteopenia (low bone mass) in males compared to females.

use of the low density software. With advancing age and
bone size, the standard analysis algorithm is sufficient in
children, but no guidelines were provided for the transition
from low to standard analysis modes. Furthermore, use of
the low density option yielded results that were not
comparable to published reference ranges. Similarly, a
paediatric whole body option was recommended for
children below age 10 years, with no provision for children
who transition across these age ranges in longitudinal
studies. Ultimately, newer weight-based algorithms were
developed for both the spine and whole body scans so that
there was a smooth transition across age ranges and a
gradual change in the bone edge detection algorithm
(Shypailo and Ellis 2005). However, these important
improvements in bone edge detection and BMC and
aBMD determination meant that previous reference ranges
based on older software and hardware were no longer
applicable.
To keep pace with the changes in paediatric software
developments, a new set of reference curves were created
based on data collected as part of unrelated research
protocols involving healthy children from five centres in the
US (Kelly et al. 2005). These included children from
Cincinnati Children’s Medical Center, Children’s Hospital of
Philadelphia, University of Utah, University of South
Dakota, and the University of California San Francisco.
This reference data set was FDA approved and has been the
basis for paediatric reference ranges on Hologic devices until
very recently. These curves were developed using the LMS
method (Cole and Green 1992) and accounted for the skew
in bone measures during childhood. However, this sample
included a large number of Hutterites from the University of
South Dakota studies, a group living in socially isolated
farming communities and known to have high bone density
q Informa UK, Ltd.
(Wey et al. 2009). Of note, only children of European
ancestry were included in these curves in accordance with
the official positions of the International Society for Clinical
Densitometry at that time (Leib et al. 2004).
In response to the need for adequate paediatric bone
mineral density reference ranges for clinical assessment, the
US National Institute of Child Health and Human
Development conducted the first multi-centre paediatric
bone density study, ‘The Bone Mineral Density in Child-
hood Study’ (BMDCS). This study used highly standardized
procedures for recruitment and data collection at five sites
in the US (Children’s Hospital of Philadelphia, Columbia
Presbyterian Hospital, NY, Cincinnati Children’s Hospital
Medical Center, Creighton University, Omaha, and LA
Children’s Hospital). The sample consisted of 2014 children,
aged 5 – 19 years at enrolment, who were evaluated annually
for up to 7 years. Scan acquisition procedures (equipment,
positioning) were highly standardized and scans were
centrally analysed. The resulting curves, generated using the
LMS method, were the first truly robust set of reference
curves based on 10 000 observations. Reference ranges for
multiple skeletal sites were based on the same group of
children, permitting comparison of bone measurements at
different sites (Zemel et al. 2011).
One of the major accomplishments of this study was the
adequate representation of African Americans. African
American children have higher bone mass and density than
other groups (Bhudhikanok et al. 1996; Nelson et al. 1997;
Gilsanz et al. 1998). Among adults, separate reference ranges
are published by the US National Health and Nutrition
Examination Survey for non-Hispanic Blacks, Mexican
Americans and Whites (Looker et al. 1995, 1998). The
BMDCS created sex-specific reference curves for African
Americans and non-African Americans based on the
406 B. ZEMEL

Males
Females
120 120

100 +2 sd 100

Lumbar Spine BMC (gm)

80 80 +2 sd
0 sd
60 60 0 sd
–2 sd
40 40 –2 sd

20 20

0 0
5 10 15 20 5 10 15 20
Age (y) Age (y)

African American Non-African American

Figure 3. Both male and female children of African-American ancestry have higher bone density than non-African-American children in the Bone
Mineral Density Study (data are adapted from Zemel et al. 2011). These findings are consistent with previous studies in children and adults.

pronounced differences between these population ancestry
groups, as shown in Figure 3. The non-African American
group included people of European, Asian and Mexican
ancestry. Differences between these groups were accounted
for when adjusted for height, so these groups were
combined.
As we learned from Professor Tanner, growth charts
derived from cross-sectional survey data are different from
those based on individual longitudinal curves because of
distortions attributable to early and late maturing
individuals (Tanner and Whitehouse 1976). Prediction
equations for calculating BMC z-scores based on longi-
tudinal models taking into account age, height, weight
and population ancestry are also available (Baxter-Jones
et al. 2010).
EFFECT OF GROWTH AND PUBERTAL DEVELOPMENT
ON BONE OUTCOMES IN CHILDREN
With linear growth, bone thickness also increases, resulting
in greater BMC and aBMD as children age. Even among
children of similar age, those who are tall for age have
greater BMC and aBMD than those who are average or short
or height age, or compared to pediatric reference data
that provide age-, gender-, and height-specific Z-scores’
(Gordon et al. 2008 pp 46 –47). The BMDCS reference
curves have accompanying equations for the adjustment of
DXA outcomes for height Z-score allowing for the changing
influence of height status on bone outcomes at different ages
(Zemel et al. 2011).
The close relationship between pubertal growth and
DXA outcomes is further exemplified by the relationship
of peak height velocity to peak bone mineral accrual. The
Saskatchewan Pediatric Bone Mineral Accrual Study was the
first to demonstrate that peak total body bone accrual occurs
, 0.61 years later in males and 0.77 years later in females
than peak height velocity (Bailey et al. 1999). This study
noted that 26 –39% of total body bone accretion occurs in
the 2 years surrounding peak bone accretion (Bailey et al.
1999; Baxter-Jones et al. 2011). At peripheral sites, such as
the tibia, increases in bone mass and dimensions continue
long after bone growth has ceased (Xu et al. 2009).
4
Spine BMC for Age Z Score

for age (Zemel et al. 2010), as shown in Figure 4. This effect 2

becomes more pronounced around the ages when pubertal
development typically occurs, because taller children are 0
often earlier maturing children in the early pubertal years
and short children are often later maturing children in the
later pubertal years. Consequently, at some ages, height –2
relative to ones’ peers, expressed as a height z-score, captures
height status as well as timing of maturation. Since timing
–4
of growth and maturation varies both within and across
groups and is often a problem among children with complex
Ht Z <–1 –1<= Ht Z <=1 Ht Z >1
medical conditions, it is useful to be able to assess the impact
of height status on bone outcomes. Indeed, the International
Figure 4. Bone outcomes are associated with growth status. Spine bone
Society of Clinical Densitometry Pediatric Positions stated mineral content (BMC) for age Z-scores are greater in children who are
‘In children with linear growth or maturational delay, . . . tall for age and lower in children who are short for age based on height-
[DXA] results should be adjusted for absolute height for-age Z-scores. Data are adapted from Zemel et al. (2010).

Annals of Human Biology

 MEASURING BONE MINERAL ACCRETION DURING CHILDHOOD
The tempo of puberty has an effect on later bone
outcomes although the mechanism is unclear. Several
decades ago it was shown that adolescent boys with
constitutional delay of puberty had lower aBMD of the
radius and lumbar spine when assessed in their mid-20s
(Finkelstein et al. 1992). Subsequent studies have shown that
(1) earlier onset of puberty in both boys and girls is
associated with greater BMC and aBMD of the spine, hip,
total body and forearm at the end of puberty (Gilsanz et al.
2011); (2) earlier timing of menarche in girls was associated
with higher aBMD of the proximal femur, lumbar spine and
radius at age 20 years (Chevalley et al. 2009); and (3) using
age at peak height velocity as a marker of tempo, later
maturation was independently associated with lower
volumetric BMD and aBMD of the total body and radius,
as well as risk of fracture in young adult military recruits
in Sweden (Kindblom et al. 2006). However, in the
Saskatchewan Pediatric Bone Mineral Accrual Study
(Jackowski et al. 2011) which followed subjects to age
30 years, maturational timing was significantly associated
with later total body BMC only for females, after controlling
for age, body size and body composition. Early maturing
females had 62 ^ 16.8 grams more and late maturing
females had 50.7 ^ 15.6 grams less total body BMC than
their average maturing peers by 20 years of age, effects that
are small compared to the measurement error for DXA.
No maturational effects were found at other measurement
sites for females and no effects were observed for males after
adjusting for age, height, lean and fat mass, calcium intake,
physical activity and maturity. These findings differ from
previous studies because of the many factors included in the
statistical models and the older age of final measurements
when late-maturing individuals would have achieved peak
bone mass.
EFFECTS OF GENES AND BEHAVIOUR ON BONE
ACCRETION
Bone density is a complex trait whereby behavioural,
environmental and genetic factors influence individual
outcome. Up to 60 – 80% of the variability in osteoporosis
risk is explained by heritable factors (Krall and Dawson-
Hughes 1993; Heaney et al. 2000; Mora and Gilsanz 2003).
Familial resemblance of BMC is expressed prior to puberty
(Ferrari et al. 1998; Duren et al. 2007). Differences between
population ancestry groups further demonstrate the strong
genetic basis of variability in bone density and are evident in
childhood (Gilsanz et al. 1991; McCormick et al. 1991;
Bachrach et al. 1999). aBMD was consistently greater at all
sites for African American compared to Caucasian, Asian
and Hispanic groups in the US, while Caucasians had
greater values than Asians and Hispanics. Differences
between Asians and Caucasians may be due to differences
in bone size (Bhudhikanok et al. 1996).
Numerous specific genetic variants are known to be
related to low bone density and development of osteoporo-
sis, such as the polymorphism in the regulatory region of
the collagen 1 alpha 1 (COL1A1) gene (Grant et al. 1996).
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407
This polymorphism was associated with decreased vertebral
BMD in pre-pubertal girls; girls who were heterozygous
and homozygous for the recessive genotype had 6.7%
and 49.4% lower trabecular BMD than girls with the SS
genotype (Sainz et al. 1999). This was confirmed in another
study (Suuriniemi et al. 2006), showing that the COL1A1
SNP was associated with BMC and aBMD of the total
body, lumbar spine, and proximal femur, as well as bone
ultrasound attenuation at the calcaneus, and markers of
bone turnover in 10 – 13 year old girls. In adolescents,
polymorphisms of the oestrogen receptor, aromatase,
interleukin-6, low density lipoprotein receptor related
protein 5 (LRP5) and osteocalcin genes have also been
shown to be independent predictors of bone size, BMC or
BMD (Lorentzon et al. 1999, 2000, 2006; Gustavsson et al.
2000; Boot et al. 2004; Koay et al. 2007; Saarinen et al.
2007; Tobias et al. 2007).
Recent discoveries resulting from genome-wide associ-
ation studies in adults further confirm a genetic component
for bone density with variants at 23 loci identified (Richards
et al. 2008; Styrkarsdottir et al. 2008; Rivadeneira et al.
2009) in populations of European ancestry. To date, the
only GWAS of BMD in children revealed a single locus
near the Osterix (SP7) gene (Timpson et al. 2009), which
was also observed in the adult studies.
Despite the large heritability of osteoporosis, the
relatively small differences in BMD associated with
modifiable factors such as physical activity and diet can
have significant health consequences. Epidemiological
studies suggest that a 10% increase (equivalent to one
standard deviation) in peak bone mass at the population
level would decrease the risk of fracture later in life by 50%
(Bonjour et al. 2003). Weight-bearing physical activity,
in particular, is critical for bone growth and strength.
Children who are non-ambulatory such as those with severe
quadriplegic cerebral palsy have significantly reduced leg
growth, compromised bone density and are at increased risk
of lower limb fractures (Henderson et al. 2009). Early studies
in healthy children demonstrated the association between
reported physical activity and aBMD (Grimston et al. 1993;
Slemenda et al. 1994; Boot et al. 1997) and athletes, such
as gymnasts (Cassell et al. 1996; Ward et al. 2005) and
tennis players (Haapasalo et al. 2000; Bass et al. 2002;
Ducher et al. 2006) have increased bone density, dimensions
and strength during growth. Physical activity intervention
programmes show that modest increases in weight-bearing
physical activity yield significant improvements in bone
density and strength (McKay et al. 2000; MacKelvie et al.
2003; Macdonald et al. 2007; Gunter et al. 2008; Hasselstrom
et al. 2008). The Saskatchewan Pediatric Bone Mineral
Accrual Study demonstrated the long-lasting effects of
physical activity during growth; they found that active males
had 8 – 13% and active females had 8 – 15% greater BMC
in adolescence than inactive peers and most of this diff-
erence was maintained into young adulthood (Baxter-Jones
et al. 2008).
Dietary factors also influence bone accretion. Calcium is
the major component of bone, with 32% of total body bone
408 B. ZEMEL
mineral as calcium (Ellis et al. 1996). Calcium supplemen-
tation studies in children showed increased bone density
with modest effects (, 3% increase) (Johnston et al. 1992;
Lee et al. 1995; Carter and Whiting 1997). Follow-up of
participants in supplementation studies indicated that the
effects of calcium supplementation are transient (Lee et al.
1996). However, dietary fortification with dairy sources of
calcium may have a more long-lasting effect in promoting
increased bone density during childhood (Bonjour et al.
1997; Cheng et al. 2005). Other nutrients are also important
for bone density, but their effects in children are less well-
studied. These include vitamin D and K, copper, protein,
phosphorous, magnesium, manganese, zinc, energy and
iron (Heaney 1988; Bounds et al. 2005; Prentice et al. 2006).
Protein has also been shown to be an important
macronutrient for bone health in adults (Dawson-Hughes
2003; Kerstetter et al. 2003, 2005) and children (Alexy et al.
2005; Vatanparast et al. 2007; Chevalley et al. 2008).
Further studies in children are needed to elucidate the effects
of specific nutrients and dietary patterns on bone
metabolism.
SUMMARY AND CONCLUSIONS
Studies of bone mineral accretion over the past two
decades have increased our fundamental understanding of
the growth of the human skeleton, brought attention to
the public health relevance of lifelong skeletal health,
and has led to the development of clinically useful tools for
the assessment of bone health during childhood. The history
of the many challenges that were met in addressing the
unique needs of bone density assessment in growing
children is a story that parallels (and was inspired by)
the work of Professor Tanner—the meticulous attention
to measurement, development of excellent reference data
and the expanding understanding of how growth, deve-
lopment, genetics and lifestyle influence the growing
skeleton.
Declaration of Interest: The author reports no conflicts of
interest. The author alone is responsible for the content
and writing of the paper.
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